Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Singapore 138648, Singapore.
Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
Cell Rep. 2018 Dec 11;25(11):3099-3109.e3. doi: 10.1016/j.celrep.2018.11.059.
Inflammation-induced disappearance of tissue-resident macrophages represents a key pathogen defense mechanism. Using a model of systemic blood-stage malaria, we studied the dynamics of tissue-resident macrophages in multiple organs to determine how they are depleted and refilled during the course of disease. We show that Plasmodium infection results in a transient loss of embryonically established resident macrophages prior to the parasitemia peak. Fate-mapping analysis reveals that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche predominantly through self-renewal. Interestingly, the local microenvironment of the spleen and liver can "imprint" the molecular characteristics of fetal-derived macrophages on newly differentiated bone marrow-derived immigrants with remarkably similar gene expression profiles and turnover kinetics. Thus, the mononuclear phagocytic system has developed distinct but effective tissue-specific strategies to replenish emptied niches to guarantee the functional integrity of the system.
炎症诱导组织驻留巨噬细胞消失代表了一种关键的病原体防御机制。我们使用全身性血期疟疾模型，研究了多个器官中组织驻留巨噬细胞的动态变化，以确定它们在疾病过程中是如何被消耗和补充的。我们发现，在寄生虫血症高峰之前，疟原虫感染导致胚胎期建立的驻留巨噬细胞短暂消失。命运图谱分析显示，炎症性单核细胞有助于补充脾红髓巨噬细胞和肝枯否细胞中空置的龛位，而肺肺泡巨噬细胞主要通过自我更新来填充其龛位。有趣的是，脾和肝的局部微环境可以将胎儿衍生的巨噬细胞的分子特征“印记”在新分化的骨髓衍生的移民上，其基因表达谱和周转率动力学非常相似。因此，单核吞噬细胞系统已经发展出独特但有效的组织特异性策略来补充排空的龛位，以保证系统的功能完整性。
